An avian human influenza reassortant virus that derived its genes for the surface glycoproteins from the human influenza A/Washington/897/80 (H3N2) virus and its six other genes from the avian influenza A/Mallard/6750/78 virus was safe satisfactorily attenuated, and non-transmissible in adult volunteers. A reassortant virus that derived only its PB1 and M genes from the ca donor was prepared from the cold adapted (ca) A/Ann/6/60 donor and the A/Washington/80 (H3N2) virus. This reassortant virus was as attenuated as another reassortant that contained all six "internal" genes of the ca donor virus. This suggests that the ca PB1 and M genes contribute to attenuation of ca reassortant viruses for humans. Reassortant ca vaccines containing the six internal ca genes induced resistance to challenge with wild type virus that was demonstrable 6 months later and this resistance exceeded that induced by inactivated influenza virus vaccine. A characterization of the local and serum antibody response to infection or vaccination with inactivated vaccine revealed that: 1) following primary influenza virus infection heterosubtypic ELISA antibody responses occur. 2) The serum ELISA IgA HA antibody response following infection is mostly polymeric without a secretory piece suggesting a mucosal origin. 3) 95% of volunteers receiving inactivated vaccine parenterally developed a local ELISA IgG HA antibody response.